MNPmApp: An image analysis tool to quantify mononuclear phagocyte distribution in mucosal tissues.

Mononuclear phagocytes (MNPs) such as dendritic cells and macrophages perform key sentinel functions in mucosal tissues and are responsible for inducing and maintaining adaptive immune responses to mucosal pathogens. Positioning of MNPs at the epithelial interface facilitates their access to luminally-derived antigens and regulates MNP function through soluble mediators or surface receptor interactions. Therefore, accurately quantifying the distribution of MNPs within mucosal tissues as well as their spatial relationship with other cells is important to infer functional cellular interactions in health and disease. In this study, we developed and validated a MATLAB-based tissue cytometry platform, termed "MNP mapping application" (MNPmApp), that performs high throughput analyses of MNP density and distribution in the gastrointestinal mucosa based on digital multicolor fluorescence microscopy images and that integrates a Monte Carlo modeling feature to assess randomness of MNP distribution. MNPmApp identified MNPs in tissue sections of the human gastric mucosa with 98 ± 2% specificity and 76 ± 15% sensitivity for HLA-DR+ MNPs and 98 ± 1% specificity and 85 ± 12% sensitivity for CD11c+ MNPs. Monte Carlo modeling revealed that mean MNP-MNP distances for both HLA-DR+ and CD11c+ MNPs were significantly lower than anticipated based on random cell placement, whereas MNP-epithelial distances were similar to randomly placed cells. Surprisingly, H. pylori infection had no significant impact on the number of HLA-DR and CD11c MNPs or their distribution within the gastric lamina propria. However, our study demonstrated that MNPmApp is a reliable and user-friendly tool for unbiased quantitation of MNPs and their distribution at mucosal sites.

Pharmacist prescribing within an integrated health system in Washington.

PURPOSE: Pharmacist prescribing as part of a collaborative drug therapy agreement (CDTA) within an integrated health system in Washington is described. SUMMARY: Virginia Mason Medical Center (VMMC) in Seattle, Washington, uses a team-based care model with broad-based CDTAs to provide quality patient care. The majority of patients are referred to the pharmacist after a diagnosis has been made and a clinical care plan has been started. The pharmacist manages the patient's care within his or her scope of practice as defined by state laws and further detailed by VMMC internal protocols. The pharmacist then documents in the electronic medical record the medication plan of care and other standard elements based on provider note templates. Medication prescribing and laboratory test ordering are the responsibilities of the pharmacist, as are any dosage adjustments or interpretations of laboratory test results. For some chronic diseases, the pharmacist may continue to see the patient indefinitely, replacing physician visits (e.g., for warfarin management). In more episodic care, the pharmacist may see the patient, optimize drug therapy, and then transition the patient back to the referring provider (e.g., for hypertension management). Integrating the pharmacist into the team has helped achieve optimal medication outcomes and increased patient satisfaction scores. CONCLUSION: The addition of the pharmacist into a team-based care model using a CDTA helped achieve optimal medication outcomes and increased patient satisfaction scores in an integrated health system. Integration was successful due to the collaborative support from physician leadership and ongoing physician involvement. Hands-on leadership by the pharmacy department and clinic directors and the health system's adoption of Lean methodology fostered an environment for developing innovative care models.

Molecular phenotyping of a UK population: defining the human serum metabolome.

Phenotyping of 1,200 'healthy' adults from the UK has been performed through the investigation of diverse classes of hydrophilic and lipophilic metabolites present in serum by applying a series of chromatography-mass spectrometry platforms. These data were made robust to instrumental drift by numerical correction; this was prerequisite to allow detection of subtle metabolic differences. The variation in observed metabolite relative concentrations between the 1,200 subjects ranged from less than 5 % to more than 200 %. Variations in metabolites could be related to differences in gender, age, BMI, blood pressure, and smoking. Investigations suggest that a sample size of 600 subjects is both necessary and sufficient for robust analysis of these data. Overall, this is a large scale and non-targeted chromatographic MS-based metabolomics study, using samples from over 1,000 individuals, to provide a comprehensive measurement of their serum metabolomes. This work provides an important baseline or reference dataset for understanding the 'normal' relative concentrations and variation in the human serum metabolome. These may be related to our increasing knowledge of the human metabolic network map. Information on the Husermet study is available at http://www.husermet.org/. Importantly, all of the data are made freely available at MetaboLights (http://www.ebi.ac.uk/metabolights/).